Agonist-specific Ca2+ signaling systems, composed of multiple intracellular Ca2+ stores, regulate gonadotropin secretion

Ca2+ signals regulate many cellular functions, including hormone secretion. Agonist-specific Ca2+ signaling may arise from the differential mobilizati on of multiple Ca2+ stores. Although they act through the same receptor sub type, two gonadotropin-releasing hormones (sGnRH and cGnRH-II) generate qua ntifiably different Ca2+ signals in goldfish gonadotropes, suggesting that their Ca2+-dependent signaling cascades may differ. We combined electrophys iology, Ca2+ imaging, and radioimmunoassay detection of gonadotropin (GTH-I I) secretion to determine the role of intracellular Ca2+ stores in GnRH-sti mulated exocytosis. Our findings suggest that voltage-gated Ca2+ channels d o not mediate acute GnRH-signaling. Instead, both sGnRH- and cGnRH-II-stimu lated GTH-II releases are dependent on Ca2+ mobilized from TMB-8/CPA-sensit ive compartments. However, sGnRH, but not cGnRH-II, utilizes intracellular stores sensitive to caffeine and xestospongin C. We also identified a homeo static mechanism where reduced extracellular Ca2+ availability increase GTH -II release by mobilizing Ca2+ stores. Our results are the first to suggest that several classes of intracellular Ca2+ stores differentially participa te in agonist signaling and homeostasis in gonadotropes. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.